Month: July 2021

Categories : Mental HealthTags :

Psychedelic Compound Treats Depression by Growing Neural Connections

On By ModernMedia
Photo by Timothy Dykes on Unsplash

In a new study, researchers have shown that a single dose of psilocybin, a psychedelic compound with potential applications for depression, prompted long-lasting increase in connections between neurons in mice. 

For some people, psilocybin, an active compound in ‘magic mushrooms’, can produce a profound mystical experience. The psychedelic was a staple of religious ceremonies among indigenous populations of the Americas and is also a popular recreational drug. It has been the subject of some interest in treating depression. But exactly how it works in the brain and how long beneficial results might last is still unclear.
“We not only saw a 10% increase in the number of neuronal connections, but also they were on average about 10% larger, so the connections were stronger as well,” reported senior author Alex Kwan, associate professor of psychiatry and of neuroscience at Yale.

Earlier work had found promising evidence that psilocybin, as well as the anaesthetic ketamine, could decrease depression. This new study found that these compounds increase the density of dendritic spines, which are small protrusions found on nerve cells which aid in the transmission of information between neurons. The number of these neuronal connections are known to be reduced by chronic stress and depression.


Prof Kwan and first author Ling-Xiao Shao, a postdoctoral associate, imaged dendritic spines in high resolution with a laser-scanning microscope, and tracked them for multiple days in living mice. They found increases in the number of dendritic spines and in their size within 24 hours of administration of psilocybin. These changes were still evident a month later. Also, mice subjected to stress showed behavioural improvements and increased neurotransmitter activity after being given psilocybin.

It may be the novel psychological effects of psilocybin itself that spurs the growth of neuronal connections, Kwan said.

“It was a real surprise to see such enduring changes from just one dose of psilocybin,” he said.  “These new connections may be the structural changes the brain uses to store new experiences.”

Source: Yale University

Categories : CancerTags :

Aspirin Could Cut Cancer Deaths by 20%

On By ModernMedia
Photo by HalGatewood.com on Unsplash

Patients with a wide range of cancers who take aspirin as part of their treatment could have their risk of death decrease by 20%, according to a major review of existing research.

Researchers at Cardiff University carried out a huge  systematic review of 118 published observational studies in patients with 18 different cancers. Pooling the results, 250 000 patients with cancer who reported taking aspirin, which was associated with a reduction of about 20% in cancer deaths.

The review said the available body of evidence regarding its efficacy and safety “justifies its use” as a supplementary treatment in a wide range of cancers—and that patients should be made aware of this.

Lead author Professor Peter Elwood, Honorary Professor at Cardiff University who has studied the effects of aspirin for over five decades, said: “In recent years, my research team and I have been struck by the actions of aspirin on the biological mechanisms relevant to cancer—and these seem to be the same in many different cancers.

“We therefore wanted to review the scientific evidence available on the use of aspirin as an additional treatment for a wide range of cancers.

“Overall, we found that at any time after a diagnosis of cancer, about 20% more of the patients who took aspirin were alive, compared with patients not taking aspirin.”

The team took into consideration aspirin taking risks and wrote to an author on each of the papers asking about any stomach or other bleeding episodes.

A minority of patients had experienced a bleed, but no evidence of any excess deaths attributable to bleeding in the patients on aspirin was found, the review noted.

“Our research suggests that not only does aspirin help to cut risk of death, but it has also been shown to reduce the spread of cancer within the body—so-called metastatic spread,” said Prof Elwood.

“There is now a considerable body of evidence to suggest a significant reduction in mortality in patients with cancer who take aspirin—and that benefit appears to not be restricted to one or a few cancers.

“Aspirin therefore appears to deserve serious consideration as an adjuvant treatment of cancer and patients with cancer and their carers should be informed of the available evidence.

“However, we must also stress that aspirin is not a possible alternative to any other treatment.”

It started in 1974 when a research team led by Professor Elwood and Professor Archie Cochrane at the Medical Research Council’s Unit in Wales showed for the first time that taking an aspirin tablet a day reduced deaths from heart disease and stroke by about 24%.

In 1990, the finding gained global traction and was judged by the BMJ to have been one of the top 50 most important research studies published since 1945. A meta-analysis of 13 randomised controlled studies found a major adverse cardiovascular event risk reduction for statin users (12%), non-smokers (10%) and males (11%).

Prof Elwood said his original study stimulated a new phase of research work on aspirin. At the time of the report about 100 clinical research studies on aspirin were published each year—but now, in excess of 1 000 are reported each year. He said a number of new clinical trials had been set up to test aspirin treatment in several cancers and the results of these should offer further clear evidence.

“Further research into aspirin and cancer would clearly be of great value, and new studies should be encouraged, especially if focused on some of the less common cancers,” said Prof Elwood.

Source: Medical Xpress

Journal information: Peter C Elwood et al, Aspirin and cancer survival: a systematic review and meta-analyses of 118 observational studies of aspirin and 18 cancers, ecancermedicalscience (2021). DOI: 10.3332/ecancer.2021.1258

Categories : COVIDTags :

South Africa Mulls AstraZeneca Again in Light of Delta Protection

On By ModernMedia
Photo by Mika Baumeister on Unsplash

Four months after selling off one million AstraZeneca vaccine doses, South Africa is considering buying more of them to contain the spread of the Delta variant.

The Delta variant is much more transmissible than previous strains, including the beta variant. However, the government presented data on 26 June showing a 70% efficacy against it with the AstraZeneca vaccine. The vaccine, which of June 2021 comprises over 90% of all doses supplied through COVAX globally, will have a significant impact as the Delta variants spread.

The government may approach the Serum Institute of India for the shots, deputy health minister Joe Phaahla told lawmakers on Wednesday.
This would add to supplies as the health regulator considers approving Russia’s Sputnik V and China’s Sinovac inoculations, he said, adding that he hoped to secure these doses from India’s Serum Institute.

In March, also facing expiry on the doses, the government sold off its doses to the African Union after research showed the then dominant Beta variant was resistant.

In February, University of the Witwatersrand Professor of Vaccinology Shabir Madhi said the AstraZeneca vaccine had a roughly 20% efficacy in preventing mild disease from the Beta variant.

“We don’t want to go back to the original argument of whether its limited efficacy on the Beta variant was correct, to dispose of it, to sell it to other countries,” Phaahla said. “With the current information that it is quite efficacious when it comes to the Delta, it is already registered.”

A study by the University of Oxford,demonstrates that AstraZeneca’s COVID vaccine, will provide protection against the Delta and Kappa variants; formerly the ‘Indian’ variants. The study investigated the ability of monoclonal antibodies from recovered or vaccinated people to neutralise the Delta and Kappa variants. 

Neutralisation against the Delta and Kappa variants was comparable with that seen against the Alpha and Gamma variants, with no evidence of widespread antibody escape as seen with the Beta variant. These results indicate that the vaccines could be effective in real-world settings. The Phase III COV002 trial in the UK showed vaccine efficacy of 70.4% at preventing symptomatic COVID against the Alpha variant, when measured more than 14 days after a second dose.

Furthermore, a recent analysis by Public Health England showed early evidence of real-world data that two doses of AstraZeneca’s COVID vaccine are effective against the Delta variant, with similar levels of protection achieved as those seen against the Alpha variant.

Sources: BusinessTech, AstraZeneca

Categories : Immune SystemTags :

Autoimmune Problems May Cause Fibromyalgia

On By ModernMedia
Photo by Sasun Bughdaryan on Unsplash

New research has shown that many fibromyalgia syndrome (FMS) symptoms are caused by antibodies that increase the activity of pain-sensing nerves throughout the body.

The results show that fibromyalgia is a disease of the immune system, rather than the currently held view that it originates in the brain.

Characterised by widespread muskoleskeletal pain, as well as fatigue and emotional distress, fibromyalgia is estimated to affect1 in 40 people (80% of which are women). It most commonly develops between the ages of 25 and 55, although children can also get it.  

The study by Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, in collaboration with the University of Liverpool and the Karolinska Institute,, demonstrates that the increased pain sensitivity, muscle weakness, reduced movement, and reduced number of small nerve-fibres in the skin that are typical of FMS are all a consequence of patient antibodies.

The researchers injected mice with antibodies from people living with FMS and saw that the mice became more sensitive to pressure and cold, as well as displaying reduced movement grip strength. In contrast, those injected with antibodies from healthy people were unaffected, showing that patient antibodies cause at least part of the disease.

Furthermore, the mice injected with fibromyalgia antibodies recovered after a few weeks, when antibodies had been cleared from their system. This finding strongly suggests that therapies which reduce antibody levels in patients are likely to be effective treatments. Such therapies are already available and are used to treat other disorders that are caused by autoantibodies.

Primary investigator Dr David Andersson, from King’s IoPPN said: “The implications of this study are profound. Establishing that fibromyalgia is an autoimmune disorder will transform how we view the condition and should pave the way for more effective treatments for the millions of people affected. Our work has uncovered a whole new area of therapeutic options and should give real hope to fibromyalgia patients.

“Previous exploration of therapies has been hampered by our limited understanding of the illness. This should now change. Treatment for FMS is focussed on gentle aerobic exercises, as well as drug and psychological therapies designed to manage pain, although these have proven ineffective in most patients and have left behind an enormous unmet clinical need.”

Dr. Andreas Goebel, the study’s principle clinical investigator from the University of Liverpool said, “When I initiated this study in the UK, I expected that some fibromyalgia cases may be autoimmune. But David’s team have discovered pain-causing antibodies in each recruited patient. The results offer amazing hope that the invisible, devastating symptoms of fibromyalgia will become treatable.”

Professor Camilla Svensson, the study’s primary investigator from Karolinska Institute said, “Antibodies from people with FMS living in two different countries, the UK and Sweden, gave similar results, which adds enormous strength to our findings. The next step will be to identify what factors the symptom-inducing antibodies bind to. This will help us not only in terms of developing novel treatment strategies for FMS, but also of blood-based tests for diagnosis, which are missing today.

Dr Craig Bullock, Research Discovery and Innovations Lead at Versus Arthritis said: “This research shows that antibodies found in human blood can cause fibromyalgia-like symptoms in mice, suggesting that these antibodies play a crucial role in the condition. Further research is needed but this offers hope to the millions of people with fibromyalgia that an effective treatment could be found in the relatively near future.”  

Source: Medical Xpress

Journal information: More information: Andreas Goebel et al, Passive transfer of fibromyalgia symptoms from patients to mice, Journal of Clinical Investigation (2021). DOI: 10.1172/JCI144201

Categories : Hospitals Medical Research & TechnologyTags :

Research Shows Surgical Simulation Training Improves Performance

On By ModernMedia
Photo by Tim Cooper on Unsplash

Success with independent surgical simulation training has made it the new normal for students at the Pan Am Clinic.

Traditionally, surgical resident training has been master–apprentice-type relationship, with gradually increasing responsibilities until the trainees can do procedures on their own. Given recent pressures in the health care system, including reduced operating room time, increased difficulty of procedures and working hour restrictions, there is less time for residents to learn using the traditional method.

Surgical simulation, a surprisingly old system, dates back nearly 2500 years, when they were first used to plan innovative procedures while maintaining patient safety. One of the first recorded instances of surgical simulation was the use of leaf and clay models in India around 600 BC to conceptualise nasal reconstruction with a forehead flap

In a recent study, researchers from the University of Manitoba and the Pan Am Clinic recently examined the effectiveness of a mixed reality simulator for the training of arthroscopy novices.

Study author Dr Samuel Larrivée said: “Sports surgeons at our institution noted anecdotally that junior residents had difficulty reaching competency in arthroscopic skills by the end of their three-month rotation, and were not as prepared when starting their senior rotation. There was a need to increase training opportunities outside of the operating room in order to prepare our residents for independent practice.”

Prior to obtaining the ArthroS™ simulator, the University of Manitoba Orthopedic Surgery program occasionally made use of options such as benchtop dry simulators, cadavers and an older generation simulator with active haptics. These largely complemented academic teaching sessions in small groups with some success, and were available for use by residents as needed. But, due to the low fidelity and difficult setup, few residents took advantage of it.

However, medical students readily took to the ArthroS simulator. Alisha Beaudoin, a co-author and medical student, attested to her experience using the ArthroS simulator in her early training. “I found this training to be very helpful during my surgery rotation. Many of my preceptors were impressed by my superior arthroscopic and laparoscopic skills. This training may allow students with an interest in surgery to be more prepared.

“Recently, many Canadian universities have moved to competency-based curriculums where residents must demonstrate competency prior to moving to the next defined practice level. The study noted that this is similar to the training available on VirtaMed ArthroS and that “a user enrolled in the mentoring program is progressed through various levels of training by meeting training targets, essentially providing a proficiency-based progression.”

This paper is the first in what the authors hope is a larger body of work on validating arthroscopy simulators for resident training. There are currently plans to repeat similar studies with the other modules (hip, shoulder, and ankle), with larger sample sizes, and at different levels of training.

Participants were split into three groups: simulator training only, mentor-based training, and a control. After  four weeks, surgical performance improved among both traditional and simulator-based training groups. The study concluded that “simulator training may provide enhanced skills to improve patient safety overall, as residents may become more skilled earlier in their training, leaving more time for the mentor to teach more advanced skills.” Dr Beaudoin further explains: “I believe that simulation training should be introduced into the standardised curriculum because I believe it offers a safe space to hone your skills and improve in a stress-free environment.”

On the strength of the results, the residency programme has made it a requirement in the curriculum that residents in their sports rotation complete the self-learning modules. Dr Larrivée believes this will help residents develop their triangulation skills and memorise the steps ahead of their first surgery, and to consolidate their knowledge.

Source: VirtaMed

Categories : Obstetrics & Gynaecology Substance UseTags :

Prenatal CBD and THC Stunts Prozac Responsiveness in Offspring

On By ModernMedia
Photo by Thought Catalog on Unsplash

Scientists have found that significant amounts of THC and CBD, the two main components of cannabis enter the embryonic brain of mice in utero and impair the mice’s ability as adults to respond to fluoxetine (Prozac).

The study suggests that when the developing brain is exposed to THC or CBD, normal interactions between endocannabinoid and serotonin signaling may be diminished as exposed individuals become adults.

“Hemp-derived CBD is a legal substance in the US, and we are in a time of increasing state-level legalisation of cannabis. Therefore, use of cannabis components have increased across most levels of society, including among pregnant women. The study marks the beginning of an effort to understand the effects of THC and CBD on the endogenous cannabinoid system (ECS) in the developing brain and body,” explained Hui-Chen Lu, director of the Linda and Jack Gill Center and professor in the Department of Psychological and Brain Sciences in the IU Bloomington College of Arts and Sciences.

Researchers studied four groups of pregnant mice. Some received daily moderate doses of either THC, CBD, or a combination of equal parts THC and CBD; a control group had placebo injections throughout pregnancy. Using mass spectrometry, IU psychological and brain sciences professor Heather Bradshaw tested embryos and found that CBD and THC both could cross the placenta and reach the embryonic brain.

“The surprising part is that maternal exposure to CBD alone — a drug that is often considered as safe and harmless and is a popular ‘natural’ therapy for morning sickness — resulted in a lasting impact on adult mice offspring,” Lu said. “Both prenatal THC and CBD exposure impaired the adult’s ability to respond to fluoxetine. The results suggest taking a cautious approach to using CBD during pregnancy.”

There is however some evidence for CBD’s effectiveness in treating chronic pain and anxiety, though currently the only FDA-approved indication for CBD is the treatment of severe seizure disorders.

“We still know very little about the effects of CBD on the developing brain,” Prof Lu said.

The new paper is one of the first studies to see the potential negative impact of CBD on the developing brain and later behaviours. However observational studies in the 1980s saw increased anxiety and depression in offspring of mothers who used the lower-strength cannabis available at the time. Since women may take cannabis products for nausea and vomiting, this has relevance for public health awareness.

Study co-author Ken Mackie, Gill Chair of Neuroscience at IU Bloomington, said researchers know that prenatal cannabis exposure may increase the risk for anxiety and depression, so it is important to evaluate the response to a class of drug used to treat anxiety and depression.

Though normal mouse behaviours were seen in many tests, one test — to determine their response to stress — had a strongly atypical result. In all groups, the mice responded normally to a stressful situation. As expected, fluoxetine increased stress resilience in mice whose mothers had received the placebo. However, the drug was ineffective in mice whose mothers had received THC, CBD or their combination.

Fluoxetine works by increasing the amount of serotonin available at brain synapses, an effect known to require the endocannabinoid system. This internal system of receptors, enzymes and molecules both mediates the effects of cannabis and plays a role in regulating various bodily systems, such as appetite, mood, stress and chronic pain.

To test if maternal exposure to THC and/or CBD impaired endocannabinoid signaling in the adult offspring, the researchers tested whether boosting the ECS with a drug would restore fluoxetine’s effectiveness. They found that the ECS boosting restored normal fluoxetine responses in mice that had received THC or CBD while their brains were developing.

Source: Indiana University

Journal reference: de Sousa Maciel, I., et al. (2021) Perinatal CBD or THC Exposure Results in Lasting Resistance to Fluoxetine in the Forced Swim Test: Reversal by Fatty Acid Amide Hydrolase Inhibition. Cannabis and Cannabinoid Research. doi.org/10.1089/can.2021.0015.

Categories : Ageing Diet and NutritionTags :

Sense of Smell Loss Uneven in Elderly

On By ModernMedia
Photo by Thought Catalog on Unsplash

Contrary to previously held scientific belief, the declining sense of smell in older people is not uniform, and their liking of many smells remains the same. Researchers at the University of Copenhagen reached this conclusion after examining a large group of older Danes’ and their intensity perception of common food odours.

The decline in smell has been demonstrated scientifically. Sense of smell gradually begins to decline from about the age of 55, and 75% of those over 80 show major olfactory impairment. While it was previously believed that one’s sense of smell broadly declined with increasing age, a study from the University of Copenhagen reports that certain food odours are significantly more affected than others.

Eva Honnens de Lichtenberg Broge and her fellow researchers tested the ability of older Danes to perceive everyday food odours. The researchers measured how intensely older adults perceived different food odours — as well as how much they liked the odours.

“Our study shows that the declining sense of smell among older adults is more complex than once believed. While their ability to smell fried meat, onions and mushrooms is markedly weaker, they smell orange, raspberry and vanilla just as well as younger adults. Thus, a declining sense of smell in older adults seems rather odor specific. What is really interesting is that how much you like an odour is not necessarily dependent on theintensity perception,” observed Eva Honnens de Lichtenberg Broge.

For example, liking seemed to be largely unaffected for fried meat, onions and mushrooms, despite the largest decline in intensity perception was seen for these specific odors. The ability to smell coffee declined, among other things, though they didn’t like the aroma of coffee to the same degree as younger adults.

The test subjects included 251 Danes between the ages of 60 and 98 and a younger group consisting of 92 people between the ages of 20 and 39.

Everyday food odours

Instead of using odours of chemical origin, which is commonly the procedure when testing the sense of smell, Eva Honnens de Lichtenberg Broge developed a test kit including 14 natural food odours familiar from everyday life, including bacon, onions, toast, asparagus, coffee, cinnamon, orange and vanilla. The odours, mainly made from essential oils, were presented to participants by sniffing sticks.

The food odours were chosen based upon commonly consumed foods and dishes that older people often eat and enjoy most according to meal plans and surveys from a Danish catering company that provides food for the elderly.

What’s the story?

The researchers can only speculate as to why the declining sense of smell in older adults seems to be odours specific, especially for savoury food smells and why, in some cases, liking is largely unaffected. 

“This may be due to the fact that these are common food odours in which saltiness or umami is a dominant taste element. It is widely recognised that salty is the basic taste most affected by aging. Since taste and smell are strongly associated when it comes to food, our perception of aroma may be disturbed if one’s taste perception of saltiness is impaired to begin with,” Eva Honnens de Lichtenberg Broge suggested.

Nutriton and quality of life

The researchers hope that their findings will help improve nutrition for the elderly. While the sense of smell is important for stimulating appetite and our serotonin levels as well, according to Eva Honnens de Lichtenberg Broge, their study demonstrates that the sensitivity of one’s sense of smell need not be decisive — participants’ liking of certain foods remained unchanged.

“Our results show that as long as a food odour is recognisable, its intensity will not determine whether or not you like it. So, if one wants to improve food experiences of older adults, it is more relevant to pay attention to what they enjoy eating than it is to wonder about which aromas seem weaker to them,” concluded Eva Honnens de Lichtenberg Broge.

Source: University of Copenhagen – Faculty of Science

Journal information: de Lichtenberg Broge, E.H., et al. (2021) Changes in perception and liking for everyday food odors among older adults. Food Quality and Preference. doi.org/10.1016/j.foodqual.2021.104254.

Categories : Medical Research & TechnologyTags :

A Step to Towards Electrically Restoring Oral Sensation and Function

On By ModernMedia
Photo by Maria Lysenko on Unsplash

In an effort towards restoring oral functionality lost to nerve or brain damage, researchers at Texas A&M University have determined the minimum electrical stimulation needed to provide sensation in various parts of the mouth.

Sensorimotor feedback loops involve the brain interpreting incoming signals from sensory nerves and then ordering motor nerves to execute a particular movement. Sensorimotor loops play a vital role in voluntary functions, like walking or holding an object, and involuntary movements, like sneezing or blinking.

Within the mouth, both sensory and motor nerves are richly supplied. In particular, sensorimotor nerves in the soft palate and tongue coordinate several intraoral movements related to swallowing, speech and respiration. Damage to either the sensory or motor nerve fibres due to neurotrauma or disease can therefore compromise these essential functions and worsening the quality of life for afflicted individuals.

Electrical nerve stimulation might help jumpstart the nerves into action, much like how a pacemaker can electrically stimulate nerves in the heart, causing the heart muscle to contract. Unlike a pacemaker however, the parameters of the electrical currents needed for proper stimulation of different parts of the mouth have not been investigated.

“Electrical stimulation can modulate nerve currents or action potentials, which are the mode of communication to and from the brain,” said Hangue Park, assistant professor in the Department of Electrical and Computer Engineering. “And so, electrical stimulation should be carefully applied, because if not, then it might cause undesirable effects, or it might not stimulate anything at all.”

To investigate the minimum stimulation currents needed, Park and his team place tiny metal electrodes in a standard dental retainer. These electrodes were positioned in subjects’ mouths to stimulate either their soft palate or the side and tip of the tongue, which are dense in sensory nerves. The researchers slowly changed the amplitude of the stimulation current, keeping the frequency fixed. Subjects reported when they began feeling a sensation and when the sensation was uncomfortable, and the same experiment was repeated with a higher frequency of current.

After compiling their data, the team determined the average perception and discomfort thresholds for the tongue and soft palate. In addition, they produced an equivalent circuit of the intraoral cavity to duplicate the electrical properties of that area. This circuit, the researchers said, can help to further study the effects of electrical stimulation offline without requiring human subjects.

The researchers noted that their next steps would be to electrically stimulate the intraoral region and investigate how these simulations change chewing, swallowing and other behaviours.

“Sensorimotor systems can be extremely vulnerable to damage due to neural defects, aging and neurodegenerative diseases,” Park said. “In this study, we have begun to lay the groundwork for electrically stimulating parts of the mouth that control involuntary and voluntary movements. Our work is a seminal study and it is important so that we can, in the near future, help people that face enormous challenges doing everyday tasks that we take for granted.”

Source: Texas A&M University

Journal information: Park, B., et al. (2021) Electrical Characterization of the Tongue and the Soft Palate using Lumped-Element Model for Intraoral Neuromodulation. IEEE Transactions on Biomedical Engineering. doi.org/10.1109/TBME.2021.3070867.

Categories : Cardiovascular DiseaseTags :

Cardiac Surgery Guidelines Updated with Emphasis on Patient Blood Management

On By ModernMedia
Photo by JAFAR AHMED on Unsplash

Newly updated multi-society cardiac surgery guidelines have shifted to a comprehensive blood management approach, with no longer simple recommendations on transfusion.

An update to the 2011 recommendations from the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists, now in collaboration with the American Society of ExtraCorporeal Technology, and the Society for the Advancement of Patient Blood Management (SABM), has been put out. It is available online in the Annals of Thoracic Surgery.

Since the last version, there has been so much new evidence that Pierre R. Tibi, MD, of Yavapai Regional Medical Center in Prescott, Arizona, and colleagues revised or added 23 recommendations and scrapped others.

Probably the biggest change is going from ‘blood conservation’ to the broader ‘patient blood management‘ (PBM) approach, Dr Tibi told MedPage Today.

“Basically we’re considering blood as another vital organ,” he said. “Why that is important is because now we look at a patient’s blood system as an organ that needs to be assessed and treated for the sake of that organ and not simply to decide when or when not to transfuse.”

Recommendations range from preoperative assessment of bleeding risk and anaemia to intraoperative perfusion and blood salvage practices to postoperative treatment with human albumin for volume replacement.

“Most hospitals around the U.S. are acutely aware of patient blood management and, to some degree or another, are implementing many of the things we are talking about,” noted Tibi, who is the most recent past president of SABM. Nationwide, the amount of blood transfused in cardiac surgery has dropped 45% in the past 10 to 15 years but still ranges widely across centres.

A broadly endorsed guideline like this emphasising the importance of a whole-patient strategy should hopefully standardize effective practices and move insurers to cover them, he suggested.

The guideline, for example, gives preoperative assessment of anaemia and its treatment with IV iron and erythropoietin-stimulating agents, if there is time, a class IIA endorsement. Anaemia is widespread, with possibly as many as 40% of patients having it, with one in 10 being under the 8 mg/dL haemoglobin threshold.

“There is a distinct correlation between preoperative anemia and worse clinical outcomes in most studies,” the guidelines note. “Usually, the greater the anemia, the more severe the complications.”

However, preoperative anaemia is “very, very underrecognised and undertested,” Dr Tibi said. While there isn’t always time to reverse anaemia that is found before cardiac surgery, he pointed out that “most of the factors in elective heart surgery have to do with insurance and Medicare. … Oftentimes the treatment for anaemia is not covered by various entities and is too expensive for patients to cover themselves.”

Other notable updates included a class IA recommendation for red blood cell salvage with centrifugation when patients are on cardiopulmonary bypass and the addition of recommendations for the assessment and treatment of patients on anticoagulants.

The guideline, for example, says to withdraw ticagrelor (Brilinta) at least 3 days, clopidogrel (Plavix) 5 days, and prasugrel (Effient) 7 days prior to elective cardiac surgery, while other non-vitamin K oral anticoagulants (NOACs) should be stopped at least 2 days in advance.

“Despite their advantages, NOACs present some periprocedural challenges for operations with a high-risk bleeding profile,” the document says. “Available measurement assays to assess anticoagulation for NOACs are imprecise, and the availability of reversal agents is limited.”

If point-of-care testing with thrombin clotting time is available for dabigatran (Pradaxa), or anti-factor Xa assays for apixaban (Eliquis) and rivaroxaban (Xarelto), in the case of emergent surgery, the guidelines recommend their use.

Source: MedPage Today

Journal information: Tibi P, et al “STS/SCA/AmSECT/SABM update to the clinical practice guidelines on patient blood management” Ann Thor Surg 2021; DOI: 10.1016/j.athoracsur.2021.03.033.

Categories : Mental Health Substance UseTags :

The Delicate Balance of the Endocannibinoid Pathway

On By ModernMedia
Photo by CRYSTALWEED cannabis on Unsplash

Scientists have uncovered an unexpected link between a synapse protein that has been implicated in neuropsychiatric disorders and the endocannabinoid pathway.

These findings suggest a role for the endocannabinoid system in conditions including bipolar disorder, according to Peter Penzes, PhD, the Ruth and Evelyn Dunbar Professor of Psychiatry and Behavioral Sciences, professor of Physiology and Pharmacology, and senior author of the study.

“The endocannabinoid system could be disrupted in patients with bipolar disease, or it could be the opposite: medical marijuana could have therapeutic potential for these patients,” said Prof Penzes, who is also director of the Center for Autism and Neurodevelopment. “These are the questions that need to be answered.”

Cannabis mimics naturally occurring endocannabinoids in the brain, which is how it produces its effect in humans. Since the specific function of endocannabinoids is still not fully understood, the legalisation of marijuana in many US states has prompted more investigation into its biological pathways, Prof Penzes said. The endocannabinoid system is a widespread neuromodulatory system that plays important roles in central nervous system (CNS) development, synaptic plasticity, and the response to endogenous and environmental insults.

Endocannabinoids are produced by an enzyme known as diacylglycerol lipase alpha (DAGLA), which is concentrated in synapses. Endocannabinoids dampen synaptic strength, which is why marijuana has calming effects.

Prof Penzes and colleagues have previously studied ankyrin-G, another synapse protein which regulates transmission speed across synapses. Aberrant over- or under-expression of ankyrin-G has been associated with disorders such as bipolar disorder, schizophrenia and autism.

Studying mice with ankyrin-G genetically deleted, they made a surprising discovery: Ankyrin-G seemed to stabilise DAGLA at synapses, increasing the efficiency of DAGLA.

“It’s a delicate mechanism that regulates dendritic spine morphology,” said lead author Sehyoun Yoon, PhD, research assistant professor of Physiology.

These findings comport with another recent study, led by investigators at Icahn School of Medicine at Mount Sinai and published in Nature Genetics. The study showed that both DAGLA and ankyrin-G (ANK3) are risk genes for bipolar disorder in a genome analysis of over 40,000 patients.

“It’s almost like somebody who is leading a double life, Dr. Jekyll and Mr. Hyde,” Prof Penzes said. “Ankyrin-G has this entire separate function.”

The convergence of ankyrin-G with the endocannabinoid pathway opens up an entire new world of possibilities, both for investigating disease risk and possible therapies.

“Cannabis may contribute to increased risk for mental disorders, which has actually been shown in schizophrenia,” Prof Penzes said. “Conversely, cannabis could be beneficial in some brain disorders, which prompted trials of medical marijuana in patients with autism.”

Prof Penzes said in future he plans to examine the downstream effects of this biological pathway, both in normal subjects and in disease.

Source: Northwestern University

Journal information: Sehyoun Yoon et al, cAMP Signaling–Mediated Phosphorylation of Diacylglycerol Lipase α Regulates Interaction With Ankyrin-G and Dendritic Spine Morphology, Biological Psychiatry (2021). DOI: 10.1016/j.biopsych.2021.03.023